Yokenella regensburgei, a novel pathogen in farmed American alligators

Increased acute mortality of farmed American alligators ( Alligator mississippiensis) was observed in various pens from 2 different farms in Louisiana over 2 years (2019-2021). A total of 14 alligators from multiple events of increased mortality were subjected to postmortem investigations. Except for one alligator with acute neurologic signs, no premonitory signs were observed. All animals had pneumonia (14/14), coelomitis (14/14), and intravascular short Gram-negative bacilli (14/14). Myocarditis (13/14) was common. Yokenella regensburgei was isolated from all alligators tested (13/13). These data suggest the respiratory tract may be a primary target system and could be involved in transmission, either through exhaled bacteria or through swallowing of contaminated respiratory fluids with passage through the feces. Available sensitivity data for Y. regensburgei in this study indicates in vitro sensitivity to aminoglycosides, fluoroquinolones, chloramphenicol, and trimethoprim/sulphamethoxazole antibiotics. Yokenella regensburgei should be included in the differential diagnosis of septicemia and acute death in alligators.

Global Distributions of Clarireedia Species and their In Vitro Sensitivity Profiles to Fungicides

Dollar spot is reported to be caused by multiple Clarireedia species and is a serious problem on many turfgrasses around the world. To our knowledge, the distribution of different Clarireedia species and their sensitivity profiles to fungicides remains unknown. In this study, a total of 275 isolates were characterized by ITS sequence. Amounts of 124, 59 and 75 isolates were identified as C. jacksonii, C. monteithiana and C. paspali, respectively, while each species of C. homoeocarpa and C. bennettii had only five isolates. Four and three isolates were identified as two potential new species, which remained to be further characterized. C. jacksonii and C. monteithiana were distributed worldwide, while C. paspali was restricted to China. Of the isolates with host information, 81% (93/115) and 19% (22/115) of C. jacksonii isolates were collected from C3 and C4 plants, respectively, 97% (56/58) of the C. monteithiana isolates were collected from C4 plants and all C. paspali isolates were collected from C4 plants. The coexistence of different Clarireedia species on the same C4 host type in the same locales was found in Shanghai (Paspalum vaginatum), Jiangsu (Paspalum vaginatum) and Florida (Cynodon dactylon). The study revealed that differential fungicide sensitivity patterns were observed in different species in Clarireedia for the first time. Similar differential sensitivity profiles were also found in the locales with coexistence of at least two species. The findings from this study suggest that the adjacent coexistence of different Clarireedia species and the differential fungicide sensitivity profiles of different species will complicate dollar spot disease control.

Ethnobotanical Survey and Evaluation of Anti-Salmonella Potentials of Commonly Used Plants for Typhoid Treatment in Ogbomoso, Oyo State, Nigeria

This study assessed the sensitivity of S. typhi to extracts of commonly used plants in treatment of typhoid in Ogbomoso, Oyo State, Nigeria. Ethnobotanical survey was conducted using a structured questionnaire. Powdered leaves of plants were extracted by maceration in distilled water. In vitro sensitivity of S. typhi to the extracts were assessed using agar well diffusion method. Groups of rats were infected orally with 0.5 McFarland suspension of S. typhi. Bacteremia in the animals was monitored by plating on Salmonella-Shigellar agar. Biochemical parameters were determined spectrophotometrically. Histological analysis was performed using H&E staining method. S. typhi was sensitive only to P. guajava and A. indica leaf extracts. V. amygladina (90.31%) and C. papaya (92.26%) showed highest percentage inhibition of S. typhi comparable with ciprofloxacin (99.86%). Haematological parameters varied significantly (p<0.05) among the groups. Antioxidant status of rats, total protein, albumin and the corresponding globulin level increased significantly (p<0.05) in the groups treated with P. guajava and A. indica. C. papaya and C. citratus ameliorated the histopathological damages observed in the liver and intestine of S. typhi infected rats. The studied plants have direct activities against S. typhi, thus reflecting the reason for their combination in traditional system of medicine.

Postoperative endophthalmitis with and without intracameral moxifloxacin prophylaxis in a high volume surgery setting

ObjectiveThis study was conducted to understand the effects of intracameral moxifloxacin in decreasing the incidence of postoperative endophthalmitis after cataract surgery in an eye hospital with a high volume surgical load.Methods and analysisIn this single-centre, retrospective, clinical registry-based study, we compared the rates of postoperative endophthalmitis in 31 340 cataract surgery patients operated during 22 months after June 2018 who received intracameral moxifloxacin to 80 643 patients operated during 41 months before June 2018 who did not receive intracameral moxifloxacin. All patients received subconjunctival gentamycin and dexamethasone. Combined surgical procedures were excluded from the study.ResultsThere was a significant reduction (p<0.001) of postoperative endophthalmitis rates in cataract surgeries from 0.144% (116/80 643) to 0.025% (8/31 340) after initiation of intracameral moxifloxacin. Endophthalmitis rates decreased from 0.120% (12/9942) to 0.009% (1/10 787) in phacoemulsification group and from 0.147% (104/70 701) to 0.034% (7/20 553) in manual small-incision cataract surgeries. Gram-positive organisms including Coagulase-negative staphylococci (37.9%, n=11) and Staphylococcus aureus (S. aureus 34.5%, n=10) were the most common organisms isolated out of 29 culture-positive cases. 24.1% (28/116) endophthalmitis cases in group without moxifloxacin were culture positive compared with 14.3% (1/7) of cases in moxifloxacin group. 72% (n=8) of the Coagulase-negative staphylococci and 80% of S. aureus isolates (n=8) showed in vitro sensitivity to moxifloxacin.ConclusionProphylactic use of intracameral moxifloxacin injection in addition to subconjunctival gentamycin in cataract surgery is associated with a significant decrease in rates of postoperative endophthalmitis when compared with the use of subconjunctival gentamycin alone in high volume settings.

Functional precision medicine in colorectal cancer based on patient-derived tumoroids and in-vitro sensitivity drug testing.

e15567 Background: Precision oncology based on in-vitro, functional assays has potential advantages compared to the much more common molecular approach, but the clinical benefit is unknown. We here report the results from the largest prospective interventional clinical trial testing the clinical outcome in colorectal cancer patients treated with drugs showing cytotoxic effect in matched patient-derived tumoroids. Methods: This single-center, phase II trial included patients with metastatic colorectal cancer previously exposed to all standard therapies. Specimens from one to three 18-16 G core needle biopsies were manually dissected, enzymatically treated, cultivated, and incubated to form 3D spherical microtumors, i.e. tumoroids. In the assay for in-vitro sensitivity testing, the tumoroids were challenged with single drugs and combinations thereof to determine patient-specific responses. Using tumoroid screening technology (IndiTreat, 2cureX, Copenhagen, Denmark), results were generated by comparing the sensitivity of the individual patient’s tumoroids with a reference panel from other patients. The testing included standard cytostatics and drugs with proven effect in previous early-phase clinical trials, a total of 15 drugs. The primary endpoint was the fraction of patients with progression-free survival (PFS) at two months. Based on placebo arms in randomized last-line trials, a minimal relevant difference of 20% (20% to 40%) was stated. Using Simon's two-stage design, a sample size of 45 patients was calculated with at least 14 PFS at two months (significance 5%, power 90%). Results: Ninety patients were enrolled from 9/2017 to 9/2020. Biopsies from 82 patients were obtained and sent for tumoroid formation of which 44 (54%, 95% CI 42-65) were successful and at least one treatment was suggested. Thirty-four patients initiated treatment according to the response obtained in the drug assays within a median of 51 days from inclusion (IQR 39-63). The primary endpoint, PFS at two months, was met in 17 of 34 patients (50%, 95%CI 32-68). There were no radiological responses. Median PFS was 81 days (95% CI 51-112) and median OS was 189 days (95% CI 103-277). Conclusions: Precision oncology using a functional approach with patient-derived tumoroids and in-vitro drug sensitivity testing seems feasible. The approach is limited by the fraction of patients with successful tumoroid development. The primary endpoint was met, as half of the patients were without progression at two months. Further clinical studies are justified. Clinical trial information: NCT03251612.